Project Summary / Abstract: The current landscape of oncology drug development is posing a challenge to widely-accepted methods used in early-phase clinical trials. A challenge in Phase I trials of cancer treatment is determining a recommended Phase II dose (RP2D) for further testing of adoptive cell therapies. In these therapies, it may not be feasible to administer a patient’s assigned dose due to an insufficient number of cells harvested or functional heterogeneity of the product. This makes it difficult to identify a feasible dose to carry forward into middle and late development, hindering the evaluation of the therapeutic intervention. Accepted dose finding designs were developed for use in trials in which successive patient cohorts are treated at various dose levels that are selected based on the safety data from previous cohorts. This approach was appropriate in the historical paradigm in which each patient is able to receive his or her intended dose based on the dose-finding algorithm. In adoptive cell therapy, the number of cells produced may be below the assigned infusion dose identified by the dose-finding design for a given patient. This raises questions of how to assess the feasibility of the approach, while also evaluating safety. Integrating accumulated feasibility and safety data to select sequential doses for patient cohorts during dose-finding trials remains a challenge. There is need to develop dose finding designs for adoptive cell therapy that utilize feasibility data in guiding allocation and determining a maximum tolerated and feasible dose (MTFD), leading to more optimal dosing and improved patient outcomes. The overall goal of this proposal is to develop dose-finding methodology for adoptive cell therapy that formally integrates dose feasibility into the design.